The resistance of crosslinked insulin derivatives to pepsin and trypsin.
The introduction of a crosslink between the amino groups of A1-glycine and B29-lysine of the insulin molecule leads to a marked decrease in sensitivity towards pepsin. Under conditions where insulin is completely degraded over 70% of N alpha A1, N epsilon B29-(carbonyl-bis-methionyl) insulin [OC(Met)2] remain intact. The resistance increases with the length of the crosslink, i.e. oxalyl less than OC(Met)2 less than dodecanedioyl insulin. The carbonyl-bis-methionyl derivative is also stabilized against tryptic attack, but to a smaller degree.
D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents; D007328:Insulin; D007700:Kinetics; D010434:Pepsin A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism*
D003432:Cross-Linking Reagents; D007328:Insulin; D014357:Trypsin; D010434:Pepsin A